Adenoviruses (Ads) cause acute and persistent infections in a variety of human tissues, and their safety and efficacy as gene vectors for use in gene therapy is being evaluated in several clinical trials. The receptor on host cells that mediates virus adsorption is one of several factors that determines the tissue tropism of individual Ad serotypes, and may also contribute to the efficient Ad cell-entry mechanism. However, receptors have not been identified for any of the over 40 known human Ad serotypes. Identification of Ad receptors will increase our understanding of viral pathogenesis, will permit the future development of antiviral regimens directed at the receptor which might block infection, and will allow the selection of appropriate Ad serotypes for use as tissue specific vectors in gene therapy. As a first step towards the characterization of Ad receptors, we propose to clone the receptor for Ad2 (serotype 2) and characterize its structure and function on human cells. Antibodies and nucleic acids probes will be developed for biochemical characterization of the receptor and to study receptor expression in different human cell types.